scholarly journals A Uve1p-Mediated Mismatch Repair Pathway inSchizosaccharomyces pombe

1999 ◽  
Vol 19 (7) ◽  
pp. 4703-4710 ◽  
Author(s):  
Balveen Kaur ◽  
J. Lee A. Fraser ◽  
Greg A. Freyer ◽  
Scott Davey ◽  
Paul W. Doetsch
Keyword(s):  
Dna Repair ◽  
Mismatch Repair ◽  
Excision Repair ◽  
Uv Light ◽  
Initial Step ◽  
Biochemical Properties ◽  
Repair Pathway ◽  
Repair Protein ◽  
Specific Manner ◽  
Dna Repair Protein

ABSTRACT UV damage endonuclease (Uve1p) from Schizosaccharomyces pombe was initially described as a DNA repair enzyme specific for the repair of UV light-induced photoproducts and proposed as the initial step in an alternative excision repair pathway. Here we present biochemical and genetic evidence demonstrating that Uve1p is also a mismatch repair endonuclease which recognizes and cleaves DNA 5′ to the mispaired base in a strand-specific manner. The biochemical properties of the Uve1p-mediated mismatch endonuclease activity are similar to those of the Uve1p-mediated UV photoproduct endonuclease. Mutants lacking Uve1p display a spontaneous mutator phenotype, further confirming the notion that Uve1p plays a role in mismatch repair. These results suggest that Uve1p has a surprisingly broad substrate specificity and may function as a general type of DNA repair protein with the capacity to initiate mismatch repair in certain organisms.

scholarly journals The DNA repair protein NBS1 influences the base excision repair pathway

2009 ◽  
Vol 30 (3) ◽  
pp. 408-415 ◽  
Author(s):  
D. Sagan ◽  
R. Muller ◽  
C. Kroger ◽  
A. Hematulin ◽  
S. Mortl ◽  
...  
Keyword(s):  
Dna Repair ◽  
Base Excision Repair ◽  
Excision Repair ◽  
Repair Pathway ◽  
Base Excision Repair Pathway ◽  
Repair Protein ◽  
Dna Repair Protein ◽  
Base Excision

scholarly journals Rapid genome editing by CRISPR-Cas9-POLD3 fusion

2021 ◽  
Author(s):  
Ganna Reint ◽  
Zhuokun Li ◽  
Kornel Labun ◽  
Salla Keskitalo ◽  
Inkeri Soppa ◽  
...  
Keyword(s):  
Dna Repair ◽  
Genome Editing ◽  
Dna Sequences ◽  
Gene Editing ◽  
Cell Types ◽  
Cell Type ◽  
Repair Protein ◽  
Specific Manner ◽  
Dna Repair Protein ◽  
Cell Type Specific

Precision CRISPR gene editing relies on the cellular homology-directed DNA repair (HDR) to introduce custom DNA sequences to target sites. The HDR editing efficiency varies between cell types and genomic sites, and the sources of this variation are incompletely understood. Here, we have studied the effect of 450 DNA repair protein - Cas9 fusions on CRISPR genome editing outcomes. We find the majority of fusions to improve precision genome editing only modestly in a locus- and cell-type specific manner. We identify Cas9-POLD3 fusion that enhances editing by speeding up the initiation of DNA repair. We conclude that while DNA repair protein fusions to Cas9 can improve HDR CRISPR editing, most need to be optimized to the particular cell type and genomic site, highlighting the diversity of factors contributing to locus-specific genome editing outcomes.

scholarly journals An alternative eukaryotic DNA excision repair pathway.

1995 ◽  
Vol 15 (8) ◽  
pp. 4572-4577 ◽  
Author(s):  
G A Freyer ◽  
S Davey ◽  
J V Ferrer ◽  
A M Martin ◽  
D Beach ◽  
...  
Keyword(s):  
Dna Repair ◽  
Excision Repair ◽  
Uv Light ◽  
Repair Process ◽  
Dna Lesions ◽  
Repair Pathway ◽  
Cyclobutane Pyrimidine Dimers ◽  
Dna Excision Repair ◽  
Pyrimidine Dimers

DNA lesions induced by UV light, cyclobutane pyrimidine dimers, and (6-4)pyrimidine pyrimidones are known to be repaired by the process of nucleotide excision repair (NER). However, in the fission yeast Schizosaccharomyces pombe, studies have demonstrated that at least two mechanisms for excising UV photo-products exist; NER and a second, previously unidentified process. Recently we reported that S. pombe contains a DNA endonuclease, SPDE, which recognizes and cleaves at a position immediately adjacent to cyclobutane pyrimidine dimers and (6-4)pyrimidine pyrimidones. Here we report that the UV-sensitive S. pombe rad12-502 mutant lacks SPDE activity. In addition, extracts prepared from the rad12-502 mutant are deficient in DNA excision repair, as demonstrated in an in vitro excision repair assay. DNA repair activity was restored to wild-type levels in extracts prepared from rad12-502 cells by the addition of partially purified SPDE to in vitro repair reaction mixtures. When the rad12-502 mutant was crossed with the NER rad13-A mutant, the resulting double mutant was much more sensitive to UV radiation than either single mutant, demonstrating that the rad12 gene product functions in a DNA repair pathway distinct from NER. These data directly link SPDE to this alternative excision repair process. We propose that the SPDE-dependent DNA repair pathway is the second DNA excision repair process present in S. pombe.

scholarly journals Rapid genome editing by CRISPR-Cas9-POLD3 fusion

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Ganna Reint ◽  
Zhuokun Li ◽  
Kornel Labun ◽  
Salla Keskitalo ◽  
Inkeri Soppa ◽  
...  
Keyword(s):  
Dna Repair ◽  
Genome Editing ◽  
Dna Sequences ◽  
Gene Editing ◽  
Cell Types ◽  
Cell Type ◽  
Repair Protein ◽  
Specific Manner ◽  
Dna Repair Protein ◽  
Cell Type Specific

Precision CRISPR gene editing relies on the cellular homology-directed DNA repair (HDR) to introduce custom DNA sequences to target sites. The HDR editing efficiency varies between cell types and genomic sites, and the sources of this variation are incompletely understood. Here, we have studied the effect of 450 DNA repair protein - Cas9 fusions on CRISPR genome editing outcomes. We find the majority of fusions to improve precision genome editing only modestly in a locus- and cell-type specific manner. We identify Cas9-POLD3 fusion that enhances editing by speeding up the initiation of DNA repair. We conclude that while DNA repair protein fusions to Cas9 can improve HDR CRISPR editing, most need to be optimized to the cell type and genomic site, highlighting the diversity of factors contributing to locus-specific genome editing outcomes.

Physical and biochemical properties of the human DNA repair protein O6-alkylguanine-DNA alkyl-transferase (AT)

1995 ◽  
Vol 121 (S1) ◽  
pp. A16-A16
Author(s):  
K. Bender ◽  
M. Federwisch ◽  
U. Loggen ◽  
J. Thomale ◽  
M. F. Rajewsky
Keyword(s):  
Dna Repair ◽  
Biochemical Properties ◽  
Human Dna ◽  
Repair Protein ◽  
Dna Repair Protein

scholarly journals Antagonism of Ultraviolet-Light Mutagenesis by the Methyl-Directed Mismatch-Repair System of Escherichia coli

Genetics ◽  
2000 ◽  
Vol 154 (2) ◽  
pp. 503-512 ◽  
Author(s):  
Hongbo Liu ◽  
Stephen R Hewitt ◽  
John B Hays
Keyword(s):  
Escherichia Coli ◽  
Mismatch Repair ◽  
Excision Repair ◽  
Spontaneous Mutation ◽  
Repair System ◽  
Uv Mutagenesis ◽  
Repair Protein ◽  
Mismatch Repair System

Abstract Previous studies have demonstrated that the Escherichia coli MutHLS mismatch-repair system can process UV-irradiated DNA in vivo and that the human MSH2·MSH6 mismatch-repair protein binds more strongly in vitro to photoproduct/base mismatches than to “matched” photoproducts in DNA. We tested the hypothesis that mismatch repair directed against incorrect bases opposite photoproducts might reduce UV mutagenesis, using two alleles at E. coli lacZ codon 461, which revert, respectively, via CCC → CTC and CTT → CTC transitions. F′ lacZ targets were mated from mut+ donors into mutH, mutL, or mutS recipients, once cells were at substantial densities, to minimize spontaneous mutation prior to irradiation. In umu+ mut+ recipients, a range of UV fluences induced lac+ revertant frequencies of 4–25 × 10−8; these frequencies were consistently 2-fold higher in mutH, mutL, or mutS recipients. Since this effect on mutation frequency was unaltered by an Mfd− defect, it appears not to involve transcription-coupled excision repair. In mut+ umuC122::Tn5 bacteria, UV mutagenesis (at 60 J/m2) was very low, but mutH or mutL or mutS mutations increased reversion of both lacZ alleles roughly 25-fold, to 5–10 × 10−8. Thus, at UV doses too low to induce SOS functions, such as Umu2′D, most incorrect bases opposite occasional photoproducts may be removed by mismatch repair, whereas in heavily irradiated (SOS-induced) cells, mismatch repair may only correct some photoproduct/base mismatches, so UV mutagenesis remains substantial.

scholarly journals Emerging Roles of RAD52 in Genome Maintenance

Cancers ◽  
2019 ◽  
Vol 11 (7) ◽  
pp. 1038 ◽  
Author(s):  
Manisha Jalan ◽  
Kyrie S. Olsen ◽  
Simon N. Powell
Keyword(s):  
Genome Stability ◽  
Genome Integrity ◽  
Repair Pathway ◽  
Genome Maintenance ◽  
Knock Out ◽  
Repair Protein ◽  
Attractive Therapeutic Target ◽  
Dna Repair Protein ◽  
Synthetically Lethal ◽  
Knock Out Mice

The maintenance of genome integrity is critical for cell survival. Homologous recombination (HR) is considered the major error-free repair pathway in combatting endogenously generated double-stranded lesions in DNA. Nevertheless, a number of alternative repair pathways have been described as protectors of genome stability, especially in HR-deficient cells. One of the factors that appears to have a role in many of these pathways is human RAD52, a DNA repair protein that was previously considered to be dispensable due to a lack of an observable phenotype in knock-out mice. In later studies, RAD52 deficiency has been shown to be synthetically lethal with defects in BRCA genes, making RAD52 an attractive therapeutic target, particularly in the context of BRCA-deficient tumors.

scholarly journals A human ortholog of archaeal DNA repair protein Hef is defective in Fanconi anemia complementation group M

2005 ◽  
Vol 37 (9) ◽  
pp. 958-963 ◽  
Author(s):  
Amom Ruhikanta Meetei ◽  
Annette L Medhurst ◽  
Chen Ling ◽  
Yutong Xue ◽  
Thiyam Ramsing Singh ◽  
...  
Keyword(s):  
Dna Repair ◽  
Fanconi Anemia ◽  
Complementation Group ◽  
Repair Protein ◽  
Dna Repair Protein ◽  
Human Ortholog
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